title: Cyclobutane pyrimidine dimers do not fully explain the mutagenicity induced by UVA in Chinese hamster cells.
abstract: UVA generates low levels of cyclobutane pyrimidine dimers (CPDs). Here we asked the question whether CPDs could fully explain the level of mutations induced by UVA. Relative mutagenicities of UVA and UVC were calculated at equal levels of CPDs in cell lines, deficient in different aspects of repair. Survival and gene mutations in the hprt locus were analyzed in a set of Chinese hamster ovary (CHO) cell lines, i.e., wild-type, Cockayne syndrome B protein-deficient (CSB), XRCC3-deficient and XRCC1-deficient adjusted to the same level of CPDs which was analyzed as strand breaks as a result of DNA cleavage by T4 endonuclease V at CPD sites. Induced mutagenicity of UVA was approximately 2 times higher than the mutagenicity of UVC in both wild-type and XRCC1-deficient cells when calculated at equal level of CPDs. Since this discrepancy could be explained by the fact that the TT-dimers, induced by UVA, might be more mutagenic than C-containing CPDs induced by UVC, we applied acetophenone, a photosensitizer previously shown to generate enhanced levels of TT-CPDs upon UVB exposure. The results suggested that the TT-CPDs were actually less mutagenic than the C-containing CPDs. We also found that the mutagenic effect of UVA was not significantly enhanced in a cell line deficient in the repair of CPDs. Altogether this suggests that neither base excision- nor nucleotide excision-repair was involved. We further challenge the possibility that the lesion responsible for the mutations induced by UVA was of a more complex nature and which possibly is repaired by homologous recombination (HR). The results indicated that UVA was more recombinogenic than UVC at equal levels of CPDs. We therefore suggest that UVA induces a complex type of lesion, which might be an obstruction during replication fork progression that requires HR repair to be further processed.
authors.affiliation: Stockholm University, Department of Genetics, Microbiology and Toxicology, Stockholm, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Biverstål
authors.forename: Fredrik
authors.initials: F
authors.lastname: Johansson
authors.forename: Dag
authors.initials: D
authors.lastname: Jenssen
authors.forename: Klaus
authors.initials: K
authors.lastname: Erixon
mesh_terms: D000818:Animals; D016466:CHO Cells / Q000378:metabolism / Q000528:radiation effects*; D002470:Cell Survival / Q000528:radiation effects; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D004260:DNA Repair / Q000235:genetics; D045643:DNA Repair Enzymes / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D004307:Dose-Response Relationship, Radiation; D016296:Mutagenesis / Q000502:physiology / Q000528:radiation effects*; D011740:Pyrimidine Dimers / Q000378:metabolism* / Q000502:physiology / Q000528:radiation effects; D011995:Recombination, Genetic / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D014466:Ultraviolet Rays / Q000009:adverse effects; D000076105:X-ray Repair Cross Complementing Protein 1
chemical_list: D004268:DNA-Binding Proteins; C095472:ERCC8 protein, human; D011740:Pyrimidine Dimers; D014157:Transcription Factors; D000076105:X-ray Repair Cross Complementing Protein 1; C110901:X-ray repair cross complementing protein 3; C000619371:XRCC1 protein, human; D045643:DNA Repair Enzymes